Journal of pharmacological sciences最新文献_第6页

Ameliorative effects of Kir4.1 channel inhibitors on lipopolysaccharide-induced cognitive impairment via BDNF/TrkB signaling pathway Kir4.1通道抑制剂通过BDNF/TrkB信号通路改善脂多糖诱导的认知功能障碍

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-07-15 DOI: 10.1016/j.jphs.2025.07.002

Yuto Ishizaki , Saki Shimizu , Ayana Kusaka, Akane Yoshida, Naofumi Kunisawa, Yukihiro Ohno

Inwardly rectifying potassium 4.1 (Kir4.1) channels are predominantly expressed in astrocytes and considered to be involved in the pathogenesis of brain diseases, including depression and epilepsy. In the present study, we evaluated the effects of Kir4.1 channel inhibitors, VU0134992 and quinacrine, on lipopolysaccharide (LPS)-induced cognitive impairment to clarify the role of Kir4.1 channels in controlling cognitive functions. Male BALB/c mice were treated with LPS, with or without Kir4.1 channel inhibitors, for 7 days. Animals were then subjected to novel object recognition (NOR) and rota-rod tests. Immunohistochemical analyses of glia fibrillary acid protein (GFAP) and neuronal nuclei (NeuN) were also performed. Treatment of LPS clearly showed cognitive impairment in the NOR test, which accompanied elevated GFAP- and reduced NeuN-immunoreactivity in hippocampal CA1 and CA3 regions. VU0134992 and quinacrine significantly ameliorated LPS-induced cognitive impairment without affecting rota-rod performance. In addition, both Kir4.1 channel inhibitors suppressed LPS-induced astrocyte activation and attenuated neuronal damage in CA1 and CA3 regions. Furthermore, combined treatments of ANA-12, a TrkB receptor antagonist, with VU0134992 suppressed the ameliorative effects of VU0134992 on cognitive impairment and hippocampal neuronal damage. These results suggest that blockade of astrocytic Kir4.1 channels ameliorates neuroinflammatory cognitive impairment via BDNF/TrkB signaling pathway.

内纠偏钾4.1 （Kir4.1）通道主要在星形胶质细胞中表达，被认为参与包括抑郁症和癫痫在内的脑部疾病的发病机制。在本研究中，我们评估了Kir4.1通道抑制剂VU0134992和quinacrine对脂多糖（LPS）诱导的认知功能障碍的影响，以阐明Kir4.1通道在控制认知功能中的作用。雄性BALB/c小鼠用LPS（含或不含Kir4.1通道抑制剂）治疗7天。然后对动物进行新目标识别（NOR）和旋转棒测试。免疫组化分析神经胶质原纤维酸蛋白（GFAP）和神经元核（NeuN）。LPS治疗在NOR测试中明显显示认知障碍，并伴有海马CA1和CA3区GFAP-升高和neun免疫反应性降低。VU0134992和quinacrine可显著改善lps诱导的认知障碍，但不影响旋转棒的性能。此外，两种Kir4.1通道抑制剂均抑制lps诱导的星形胶质细胞活化，并减轻CA1和CA3区域的神经元损伤。此外，TrkB受体拮抗剂ANA-12与VU0134992联合治疗可抑制VU0134992对认知功能障碍和海马神经元损伤的改善作用。这些结果表明，阻断星形细胞Kir4.1通道可通过BDNF/TrkB信号通路改善神经炎性认知障碍。

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引用次数: 0

Early temporal suppression of SPARC inhibits oxidative stress, inflammation, and fibrosis in the chronic phase after renal ischemia/reperfusion 早期时间抑制SPARC可抑制肾缺血/再灌注后慢性期的氧化应激、炎症和纤维化

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-07-14 DOI: 10.1016/j.jphs.2025.07.003

Hiroe Toba , Denan Jin , Shinji Takai

Acute kidney injury is associated with not only high morbidity in the acute phase but also the development of chronic kidney disease (CKD). Recently, we found that suppression of secreted protein acidic and rich in cysteine (SPARC) exhibits renoprotective effects in acute ischemia/reperfusion (I/R) injury. The present study investigated the hypothesis that temporal suppression of SPARC in the early stages of I/R-injury might lead to the prevention of renal injury in the chronic phase. The left renal pedicle of male BALB/c mice was occluded for 45 min after right uninephrectomy and subsequently reperfused for 28 days. Small interfering RNA (siRNA) targeting SPARC was injected intravenously 1 day before and 3 days after I/R. Histological assessment revealed that SPARC knockdown by siRNA attenuated tubular injury, tubulointerstitial fibrosis, and the overexpression of 4-hydroxynonenal, a marker of lipid peroxidation. I/R-induced overexpression of a major source of superoxide NADPH oxidase, tumor necrosis factor-α, and matrix metalloproteinase-9 was suppressed by siRNA targeting SPARC. Treatment with siRNA targeting SPARC reduced the expression of a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS1), which colocalizes with SPARC. In conclusion, SPARC might be a potential therapeutic target for preventing CKD development following acute I/R injury.

急性肾损伤不仅与急性期的高发病率有关，而且与慢性肾脏疾病（CKD）的发展有关。最近，我们发现抑制酸性和富含半胱氨酸的分泌蛋白（SPARC）在急性缺血/再灌注（I/R）损伤中具有肾保护作用。本研究探讨了在I/ r损伤早期时间抑制SPARC可能导致慢性肾损伤预防的假设。雄性BALB/c小鼠右肾切除后左肾蒂封闭45分钟，再灌注28天。在I/R前1天和后3天静脉注射靶向SPARC的小干扰RNA （siRNA）。组织学评估显示，通过siRNA敲低SPARC可减轻小管损伤、小管间质纤维化和4-羟基壬烯醛（脂质过氧化标志物）的过度表达。I/ r诱导的超氧化物NADPH氧化酶、肿瘤坏死因子-α和基质金属蛋白酶-9的过表达被靶向SPARC的siRNA抑制。靶向SPARC的siRNA治疗降低了与SPARC共定位的具有血小板反应蛋白1型基序（ADAMTS1）的崩解素和金属蛋白酶的表达。总之，SPARC可能是预防急性I/R损伤后CKD发展的潜在治疗靶点。

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引用次数: 0

TPNA10168, an Nrf2 activator, attenuates LPS-induced inflammation in microglia through modulation of MAPK and NF-κB pathways TPNA10168是一种Nrf2激活剂，通过调节MAPK和NF-κB通路，减轻lps诱导的小胶质细胞炎症

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-07-03 DOI: 10.1016/j.jphs.2025.07.001

Yasuhiko Izumi , Eri Koide , Fumika Kobayashi , Saori Ikawa , Midai Takayama , Kouya Yamaki , Norihiko Takeda , Takahiro Yamada , Masafumi Ueda , Toshiaki Kume , Yutaka Koyama

The nuclear factor erythroid 2-related factor 2 (Nrf2)–antioxidant response element (ARE) pathway is a major cellular defense mechanism against oxidative stress through the induction of antioxidant proteins. Chemical inducers of Nrf2 often exhibit anti-inflammatory properties. TPNA10168, originally identified as an Nrf2–ARE activator, has previously been shown to attenuate interferon-γ-induced inflammatory responses in BV-2 microglial cells in an Nrf2-independent manner. However, its anti-inflammatory effects on primary microglia remain unclear. In this study, TPNA10168 significantly suppressed the lipopolysaccharide (LPS)-induced expression of inflammatory genes, including tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, in primary microglia. The anti-inflammatory effects of TPNA10168 persisted even after Nrf2 knockdown. Mechanistic analysis revealed that TPNA10168 inhibited LPS-induced phosphorylation of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and nuclear factor-κB (NF-κB) p65 without affecting NF-κB nuclear translocation. These findings indicate that TPNA10168 attenuates microglial activation by inhibiting proinflammatory signaling pathways, in part through Nrf2-independent pathways, and is a promising compound for modulating neuroinflammation.

核因子红细胞2相关因子2 (Nrf2) -抗氧化反应元件（ARE）通路是细胞通过诱导抗氧化蛋白抵抗氧化应激的主要防御机制。Nrf2的化学诱导剂通常表现出抗炎特性。TPNA10168最初被鉴定为Nrf2-ARE激活剂，先前已被证明以nrf2不依赖的方式减弱干扰素γ诱导的BV-2小胶质细胞炎症反应。然而，其对初级小胶质细胞的抗炎作用尚不清楚。在本研究中，TPNA10168显著抑制脂多糖（LPS）诱导的炎性基因表达，包括肿瘤坏死因子-α、白细胞介素(IL)-1β和IL-6。即使Nrf2敲低，TPNA10168的抗炎作用仍然存在。机制分析显示，TPNA10168抑制lps诱导的细胞外信号调节激酶、p38丝裂原活化蛋白激酶和核因子-κB (NF-κB) p65的磷酸化，但不影响NF-κB核易位。这些发现表明TPNA10168通过抑制促炎信号通路（部分通过nrf2非依赖性通路）来减弱小胶质细胞的激活，是一种有希望调节神经炎症的化合物。

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引用次数: 0

Formalizing and expanding our ethical framework: Introducing the comprehensive ethical guidelines for the Journal of Pharmacological Sciences 规范和扩展我们的伦理框架：为《药理学杂志》介绍全面的伦理准则

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-06-26 DOI: 10.1016/j.jphs.2025.06.007

Junko Kurokawa , Yuji Ikegaya , Tomoyuki Furuyashiki , Naohiko Anzai , Shuhei Tomita , Yasunari Kanda

引用次数: 0

SMTP-44D prevents negative symptoms of diabetic neuropathy by inhibiting sciatic nerve apoptosis SMTP-44D通过抑制坐骨神经凋亡来预防糖尿病神经病变的阴性症状

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-06-26 DOI: 10.1016/j.jphs.2025.06.006

Ayaka Aoki , Keita Shibata , Ryosuke Shinouchi , Keiji Hasumi , Koji Nobe

Diabetic neuropathy (DN) affects more than 50 % of patients with diabetes mellitus (DM). With progression, it causes negative symptoms characterized by sensory numbness. However, no effective treatment drug has been approved for the negative symptoms of DN. In this study, Stachybotrys microspora triprenyl phenol-44D (SMTP-44D), previously reported to inhibit apoptosis and ameliorate axonal damage in immortalized mouse Schwann cells treated with high glucose, was evaluated in a DN mouse model. Streptozocin (STZ)-induced DM models were treated with SMTP-44D for 49 days starting 8 days after STZ administration of SMTP-44D, and effects on mechanical and thermal thresholds, blood flow, and conduction velocity were evaluated. Epoxyeicosatrienoic acid (EET)/dihydroxyeicosatrienoic acid (DHET) measurements in serum, morphological changes in the sciatic nerve, immunohistochemistry, and TUNEL staining were performed to elucidate the mechanism of action. SMTP-44D improved the 11,12-EET/DHET decrease in serum and blood flow in the sciatic nerve. It inhibited sciatic nerve apoptosis and alleviated myelin thinning, thereby preserving the conduction velocity and showing dose-dependent improvements in mechanical and thermal threshold elevation. A hypoglycemic effect with long-term administration is suggested based on the findings. In conclusion, SMTP-44D is a promising therapeutic agent against the negative symptoms of DN.

糖尿病性神经病变（DN）影响50%以上的糖尿病（DM）患者。随着病情发展，会出现以感觉麻木为特征的阴性症状。然而，目前还没有一种有效的药物被批准用于治疗DN的阴性症状。在本研究中，研究人员在DN小鼠模型中对Stachybotrys microspora triprenyl pheno - 44d （SMTP-44D）进行了研究，该研究先前报道了SMTP-44D在高糖处理的永生化小鼠雪万细胞中抑制凋亡并改善轴突损伤。从STZ给予SMTP-44D后8天开始，用SMTP-44D治疗STZ诱导的DM模型49天，观察其对机械阈值、热阈值、血流量和传导速度的影响。采用血清环氧二碳三烯酸(EET)/二羟基二碳三烯酸（DHET）测定、坐骨神经形态学变化、免疫组化、TUNEL染色等方法探讨其作用机制。SMTP-44D改善了血清和坐骨神经血流中11,12- eet /DHET的下降。它抑制坐骨神经凋亡，减轻髓鞘变薄，从而保持传导速度，并在机械和热阈值升高方面表现出剂量依赖性改善。根据研究结果，建议长期服用具有降糖作用。综上所述，SMTP-44D是一种很有前景的治疗DN阴性症状的药物。

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引用次数: 0

Phenylalanine amide derivatives promote FLG expression via AHR activation in normal human epidermal keratinocytes 苯丙酰胺衍生物通过AHR激活在正常人表皮角质形成细胞中促进FLG表达

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-06-23 DOI: 10.1016/j.jphs.2025.06.005

Akiko Sumitomo , Ratklao Siriwach , Makio Higuchi , Quynh Anh Ngo , Nobuo Tanaka , Somsak Prasongtanakij , Dean Thumkeo , Shuh Narumiya

Filaggrin (FLG) is one of the major components expressed in terminally differentiated keratinocytes and critical for skin barrier functions. It is known that reduced FLG expression causes skin barrier dysfunctions and results in atopic dermatitis (AD). Restoring FLG expression therefore may serve as an effective therapeutic strategy against AD. Using normal human epidermal keratinocyte (NHEK), we identified a phenylalanine amide derivative, termed Compound 8.1, that promotes expression of FLG and other skin barrier-related genes in NHEKs. Gene expression profiling by microarray suggested that Compound 8.1 promotes FLG expression through activation of the aryl hydrocarbon receptor (AHR). Interestingly, compared to a typical AHR activator, FICZ (6-Formylindolo[3,2-b]carbazole), Compound 8.1 preferentially upregulated the expression of genes related to keratinocyte differentiation and skin barrier function in an AHR-dependent manner, but induced a conventional AHR target gene involved in cellular toxicity, CYP1A1, to a significantly lesser extent. Structure-activity relationship analysis further demonstrates that the structural modification of Compound 8.1 could dissociate induction of skin barrier-related gene expression from CYP1A1-dependent metabolism of xenobiotics in AHR actions. Together, our results suggest that Compound 8.1 serves as a prototype compound for developing novel AHR-activating drugs to treat skin barrier dysfunctions without toxicity.

聚丝蛋白（Filaggrin， FLG）是终分化角质形成细胞中表达的主要成分之一，对皮肤屏障功能至关重要。众所周知，FLG表达减少会导致皮肤屏障功能障碍并导致特应性皮炎（AD）。因此，恢复FLG表达可能是对抗AD的有效治疗策略。使用正常的人表皮角质细胞（NHEK），我们发现了一种苯丙氨酸酰胺衍生物，称为化合物8.1，可促进FLG和其他皮肤屏障相关基因在NHEK中的表达。基因表达谱分析表明，化合物8.1通过激活芳烃受体（AHR）促进FLG的表达。有趣的是，与典型的AHR激活剂FICZ （6-Formylindolo[3,2-b]carbazole）相比，化合物8.1以AHR依赖的方式优先上调与角质形成细胞分化和皮肤屏障功能相关的基因的表达，但诱导参与细胞毒性的传统AHR靶基因CYP1A1的程度要小得多。构效关系分析进一步表明，化合物8.1的结构修饰可以将AHR作用中皮肤屏障相关基因表达的诱导与cyp1a1依赖性外源代谢分离。总之，我们的研究结果表明，化合物8.1可以作为开发新型ahr激活药物的原型化合物，用于治疗皮肤屏障功能障碍而没有毒性。

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引用次数: 0

Medial prefrontal cortex inputs to the dorsomedial striatum regulate motivation for wheel running in male mice 内侧前额叶皮层对背内侧纹状体的输入调节雄性小鼠滚轮跑的动机

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-06-17 DOI: 10.1016/j.jphs.2025.06.004

Kazuhei Niitani , Ryoma Nishida , Yu Ogura , Naoya Nishitani, Satoshi Deyama, Katsuyuki Kaneda

Wheel running is rewarding for rodents, and thus they exhibit strong willingness to engage in it and desire for it, i.e., motivation. Although neural activity in the dorsomedial striatum (DM-Str) has been suggested to be involved in motivation for wheel running, the causal relationship between neural activity and motivation remains unknown. Here, we investigated the role of neural activity in the DM-Str and the mechanisms regulating this activity in motivation for wheel running. Fiber photometry recordings with GCaMP sensors revealed that DM-Str neural activity transiently increased at the initiation of running on running wheels (RWs), whereas it decreased during running. Intra-DM-Str injection of the GABA_A receptor agonist muscimol or the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist NBQX reduced the number of RW rotations. In the open field test, neither muscimol nor NBQX injection into the DM-Str affected locomotor activity. Additionally, selective chemogenetic inhibition of projections from the medial prefrontal cortex (mPFC) to the DM-Str reduced RW rotation numbers without altering locomotor activity. Together, our findings suggest that DM-Str neural activity, enhanced by glutamatergic projection from the mPFC, plays a critical role in regulating motivation for wheel running.

跑轮对啮齿动物来说是一种奖励，因此它们表现出强烈的参与意愿和渴望，即动机。虽然背内侧纹状体（DM-Str）的神经活动被认为与车轮运动的动机有关，但神经活动与动机之间的因果关系尚不清楚。在此，我们研究了神经活动在DM-Str中的作用，以及这种活动在车轮跑动机中的调节机制。GCaMP传感器的纤维光度记录显示，DM-Str神经活动在跑步轮（RWs）开始时短暂增加，而在跑步过程中则下降。在dm - str内注射GABAA受体激动剂muscimol或α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂NBQX可减少RW旋转次数。在野外试验中，DM-Str内注射muscimol和NBQX均不影响运动活动。此外，选择性化学发生抑制内侧前额叶皮层（mPFC）到DM-Str的投射减少了RW旋转次数，但不改变运动活动。综上所述，我们的研究结果表明，DM-Str神经活动被来自mPFC的谷氨酸能投射增强，在调节车轮跑的动机中起着关键作用。

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引用次数: 0

Down-regulation of TNF-α/RIPK/Caspase-8 axis by combined infliximab and umbelliferone prevents unilateral ureter ligation-induced interstitial renal fibrosis 英夫利昔单抗联合umbelliferone下调TNF-α/RIPK/Caspase-8轴可预防单侧输尿管结扎引起的间质性肾纤维化

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-06-16 DOI: 10.1016/j.jphs.2025.06.003

Maha Habash , Zainab H. Almansour , Rasha K. Al-Akeel , Mohammad Bani Ismail , Duaa Althumairy , Hamad Abu Zahra , Tarek Hamdy Abd-Elhamid , Osama M. Ghogar , Mahmoud M. Ali , Mostafa K. Abd El-Aziz , Elham I. Sharab , Heba F. Khader , Amany Refaat Mahmoud , Fares E.M. Ali

Obstructive nephropathy is a chronic condition that causes progressive kidney damage due to inflammation, oxidative stress, necroptosis, and fibrosis. The present study aimed to evaluate the potential chemopreventive effect of infliximab (TNF-α inhibitor) or umbelliferone (UMB, a natural antioxidant) individually and together to treat unilateral ureter ligation (UUL)-induced interstitial renal fibrosis in rats. The therapeutic effects were assessed through renal function biomarkers, histopathology, fibrosis, inflammation, oxidative stress, and necroptosis. UUL-induced renal injury led to increased serum biomarkers (urea, creatinine, uric acid), inflammation markers (TNF-α, NF-κB, IKK), oxidative stress (elevated NADPH oxidase and MDA, reduced Nrf2/HO-1, GSH, SOD), and necroptosis (upregulated RIPK1/RIPK3/p-RIPK3/MLKL/caspase-8), with substantial collagen deposition and fibrosis. Treatment with infliximab and UMB showed preventive effects by suppressing TNF-α signaling, reducing oxidative stress, and boosting antioxidant defense. Combined therapy provided superior results by downregulating TNF-α/RIPK/Caspase-8 pathways, enhancing Nrf2/HO-1 activity, reducing fibrosis, and restoring renal structure and function. Computational docking confirmed the ability of UMB to interact with TNF-α and RIPK3/MLKL binding sites. In conclusion, the combination of infliximab and UMB offers a promising multi-targeted approach to treat obstructive nephropathy and related chronic kidney diseases and highlights its potential to modulate key pathways involved in kidney fibrosis.

梗阻性肾病是一种慢性疾病，由炎症、氧化应激、坏死和纤维化引起进行性肾损害。本研究旨在评价英夫利昔单抗（TNF-α抑制剂）或伞liferone （UMB，天然抗氧化剂）单独或联合治疗单侧输尿管结扎（UUL）诱导的大鼠间质性肾纤维化的潜在化学预防作用。通过肾功能生物标志物、组织病理学、纤维化、炎症、氧化应激和坏死下垂来评估治疗效果。uul诱导的肾损伤导致血清生物标志物（尿素、肌酐、尿酸）、炎症标志物（TNF-α、NF-κB、IKK）、氧化应激（NADPH氧化酶和MDA升高，Nrf2/HO-1、GSH、SOD降低）和坏死坏死（RIPK1/RIPK3/p-RIPK3/MLKL/caspase-8上调）升高，并伴有大量胶原沉积和纤维化。英夫利昔单抗和UMB治疗通过抑制TNF-α信号、减少氧化应激和增强抗氧化防御显示出预防作用。联合治疗通过下调TNF-α/RIPK/Caspase-8通路，增强Nrf2/HO-1活性，减少纤维化，恢复肾脏结构和功能，取得了较好的效果。计算对接证实了UMB能够与TNF-α和RIPK3/MLKL结合位点相互作用。总之，英夫利昔单抗和UMB联合治疗阻塞性肾病和相关慢性肾脏疾病提供了一种有前景的多靶点方法，并突出了其调节肾纤维化关键通路的潜力。

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引用次数: 0

Automated analysis of mouse rearing using deep learning 利用深度学习对老鼠饲养进行自动分析

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-06-13 DOI: 10.1016/j.jphs.2025.06.002

Naoaki Sakamoto , Masahiro Fukuda , Yusuke Miyazaki , Keisuke Omori , Koji Kobayashi , Takahisa Murata

Rodent rearing behavior is frequently assessed as an indicator of anxiety and exploratory tendencies. This study developed a convolutional recurrent neural network (CRNN) model to detect mouse rearing using overhead videos. Behavioral data from C57BL/6 mice under light and dark conditions were manually labeled frame-by-frame and used to train the CRNN model. Model performance was evaluated on separate test videos, achieving a sensitivity of 89.2 %, comparable to human observation. The model reliably detected increased rearing following caffeine administration and distinguished differences between day and night activity patterns.

啮齿动物的饲养行为经常被评估为焦虑和探索倾向的指标。本研究建立了一种卷积递归神经网络（CRNN）模型，用于检测头顶视频中小鼠的饲养行为。C57BL/6小鼠在光照和黑暗条件下的行为数据被手工逐帧标记，并用于训练CRNN模型。在单独的测试视频上评估了模型的性能，达到了89.2%的灵敏度，与人类观察相当。该模型可靠地检测到咖啡因摄入后饲养量的增加，并区分了白天和夜间活动模式的差异。

引用次数: 0

Oral administration of undenatured type II collagen significantly inhibits arthritis-associated pain signal in a mouse model of collagen antibody-induced arthritis and meniscus removal 在胶原抗体诱导的关节炎和半月板切除小鼠模型中，口服未变性的II型胶原可显著抑制关节炎相关的疼痛信号

IF 3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of pharmacological sciences

Pub Date : 2025-06-12 DOI: 10.1016/j.jphs.2025.06.001

Ibuki Yasuda , Mao Kaneki , Chiharu Ohira , Mana Ichikawa , Eiji Iwazaki , Hirohito Tsuruwaka , Tomoki Fukuyama

Osteoarthritis (OA) is joint pain caused by persistent low-grade inflammation, and is characterized by bone remodeling, synovitis, and articular cartilage degeneration. This study focused on undenatured type II collagen (UC-II®) and examined its influence on OA-associated pain. The increased Ca²⁺ influx to typical nociceptive receptors TRPA1 and TRPV1 in the peripheral neurons of dorsal root ganglia was significantly inhibited by UC-II® treatment and similar inhibitory patterns were confirmed in vivo pain behavior tests in a mouse model of arthritis. Our findings suggest the effectiveness of UC-II® on OA-associated pain.

骨关节炎（OA）是由持续的低度炎症引起的关节疼痛，以骨重塑、滑膜炎和关节软骨变性为特征。本研究聚焦于未变性II型胶原蛋白（UC-II®），并研究其对oa相关疼痛的影响。UC-II®治疗显著抑制了背根神经节外周神经元中典型伤害性受体TRPA1和TRPV1的Ca2+内流增加，并且在小鼠关节炎模型的体内疼痛行为测试中证实了类似的抑制模式。我们的研究结果表明UC-II®对oa相关疼痛的有效性。

引用次数: 0